We are continuing our studies on the control fo alphafetoprotein (AFP) and albumin (ALB) gene expression during fetal and neonatal development, liver regeneration, tumor growth and hepatocarcinogenesis in the rat. Using radiolabeled, specific DNA probes for AFP and ALB we have chronicled the time course of appearance, disappearance and the absolute levels of these mRNA's in the above mentioned tissues. To discern possible molecular mechanisms responsible for the observed changes in transcriptional activity we will first test the hypothesis that changes in the activity of these genes is mediated through changes in the primary structure of the DNA. DNA from the various tissues will be cleaved with restriction endonucleases, electrophoresed on agarose gels and hybridized to radiolabeled probes. The rationale is that changes such as methylation, base substitutions and gene rearrangement will be reflected in altered patterns of hybridization since changes in the DNA will effect the number of cleavage sites for the highly sequence specific restriction endonucleases. We are also planning to explore AFP and ALB gene activity in fetal and neonatal tissues other than liver and yolk sac, to expand our studies on using DNA probes to establish and document the relationship between the appearance 'oval cells' and the development of hepatocellular carcinoma and, finally, to begin an investigation into the control of gene expression in a unique strain of mice characterized by elevated serum AFP levels and an inability to turn off AFP synthesis during early adulthood.